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Original Studies

Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma Versus Angle-closure Glaucoma

Lin, Michael M. MD*,†; Rageh, Abdulrahman MD*; Turalba, Angela V. MD; Lee, Hang PhD§; Falkenstein, Iryna A. MD; Hoguet, Ambika S. MD; Ojha, Pallavi MD#; Rao, Veena S. MD**; Ratanawongphaibul, Kitiya MD*,††; Rhee, Douglas J. MD‡‡; Shen, Lucy Q. MD*; Song, Brian J. MD§§; Chen, Teresa C. MD*

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doi: 10.1097/IJG.0000000000001225
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Endocyclophotocoagulation (ECP; Endo Optiks, Little Silver, NJ) was first reported by Uram1 in 1992 and delivers laser energy via an ab interno approach under direct visualization of the ciliary processes. This energy is absorbed by melanin in the pigmented ciliary body epithelium, is transferred to the inner nonpigmented ciliary body epithelium, and is then thought to lower intraocular pressure (IOP) by decreasing aqueous humor production. ECP has been embraced by some specialists as less traumatic than transscleral cyclophotocoagulation because it selectively targets the ciliary body epithelium without affecting the ciliary body muscle and stroma, a finding that has been confirmed by histologic analysis in rabbit eyes, rhesus monkey eyes, and human autopsy eyes.2–4

Uram’s initial study focused on intractable neovascular glaucoma, but later studies evaluated ECP in eyes that had failed trabeculectomy, had failed tube shunt surgery or had other advanced glaucomas.5–7 ECP initially caused complications including fibrin exudation and cystoid macular edema (CME), but these side effects became less common as surgeons used lower laser power settings. Given the improved risk profile of ECP, it has found use in eyes with better visual potential, often in combination with phacoemulsification.8–10

Combined phacoemulsification and ECP (phaco/ECP) have also found use in plateau iris to shrink the ciliary processes and to open the drainage angle, which has been confirmed by ultrasound biomicroscopy.11,12 Anecdotally, some glaucoma specialists have also chosen ECP in nonplateau iris cases of chronic angle-closure glaucoma (CACG) due to a belief that shrinkage of the ciliary processes may cause mechanical tension on the trabecular meshwork that may help to open the angle and improve drainage, similar to the putative mechanisms of pilocarpine and argon laser trabeculoplasty. However, in one study of eyes with advanced glaucoma, the success rate of phaco/ECP was higher for primary open-angle glaucoma (POAG) than for CACG, though the results did not reach statistical significance.7 To our knowledge, there have been no other large studies of whether phaco/ECP has differential efficacy in open-angle versus angle-closure glaucoma at various stages of glaucoma severity; therefore, the purpose of this retrospective chart review was to address this question.


This study was a retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution. When both eyes of a patient were eligible, the first eye that underwent phaco/ECP was chosen for analysis. Patients were required to have at least 1 year of follow-up in order to be included.

Only eyes with CACG and POAG were included in this study, and other types of glaucoma were excluded. CACG was defined as ≥180 degrees iridotrabecular contact with elevated IOP and optic neuropathy, without plateau iris angle configuration on gonioscopy. Patients with POAG had been listed as having this diagnosis by their glaucoma specialists in the medical records and were confirmed on chart review to have a history of elevated IOP, open angle on gonioscopy, and chronic, progressive optic neuropathy with characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. Pseudoexfoliation, pigmentary, and normal tension glaucoma were considered separate from POAG and were excluded.

In addition to the type of glaucoma, other historical and clinical information recorded included the following: prior laser and surgical treatments, glaucoma medications, age, sex, race and ethnicity, visual acuity (VA), refractive error, IOP, cup to disc ratio, central corneal thickness by ultrasound pachymetry, axial length, and visual field testing (Humphrey visual field analyzer 750i; Carl Zeiss Meditec Inc., Jena, Germany). Postoperative information included postoperative topical medication regimen, need for additional glaucoma procedures, and sight-threatening postoperative complications, such as CME, choroidal detachment, and vitreous hemorrhage. On the basis of the Hodapp-Parrish-Anderson staging system using visual field mean deviation, eyes were classified as having mild (better than −6 dB), moderate (−6 dB or worse but better than −12 dB), or advanced glaucoma (−12 dB or worse).13

ECP technique varied among the 9 surgeons whose charts were reviewed. Generally, after inflation of the ciliary sulcus with viscoelastic, between 180 and 360 degrees of ciliary body were treated with a curved endoscope probe with power that ranged from 150 mW to 500 mW as necessary to whiten and shrink the ciliary processes.

Study population demographic and ocular characteristics were summarized by mean±SD or counts and proportions as appropriate. General linear model was used to determine the relationship between IOP and medication reductions with categorical and continuous variables. Univariate testing was applied first to identify variables with P<0.15 for the purpose of building multivariable models, and serial elimination of variables with P≥0.15 was repeated until all variables in the final linear model had P<0.15. P<0.05 was considered statistically significant in the final analyses.


The final study population included 63 eyes of 63 patients with an average of 3.0±1.7 years of follow-up. One author (L.Q.S.) performed 38 (60.3%) surgeries, while other authors performed between 1 and 12. Postoperatively, 40 (63.5%) eyes were treated with nonsteroidal anti-inflammatory drug drops, and when treated, regimens lasted 4.2±2.5 weeks. All eyes were treated with postoperative topical steroid drops for an average of 4.9±1.3 weeks, most commonly with prednisolone acetate 1%, though 22 (34.9%) had regimens that included difluprednate 0.05%, and intravenous methylprednisolone was administered intraoperatively in 2 cases. Regimens varied among different glaucoma specialists and also among patients of the same glaucoma specialist without consistent patterns.

Table 1 summarizes study population demographic and ocular characteristics. The study population was predominantly female (61.9%) and Caucasian (68.3%). There were 41 (65.1%) eyes with POAG and 22 (34.9%) eyes with CACG. There were 23 (36.5%) eyes with mild glaucoma, 19 (30.2%) with moderate, 12 (19.0%) with advanced, and 9 (14.3%) where stage was indeterminate (Table 1).

Study Population Demographic and Ocular Characteristics

Table 2 summarizes treatment responses to ECP for the entire study population and compares outcomes between POAG and CACG. ECP was applied at a power of 271±65 mW for 296±40 degrees, and there was no difference between POAG and CACG in power or degrees treated. Baseline IOP was 17.0±5.4 mm Hg, and there were 3.6±6.4 and 3.7±6.4 mm Hg average IOP reductions at 1 year and final follow-up, respectively. There were 0.5±1.1 and 0.5±1.2 fewer medications used at 1 year and final follow-up, respectively. Average logMAR VA improved from 0.28 to 0.19, although 5 (7.9%) eyes lost 2 lines of vision. At final follow-up, 43 (68.3%) eyes achieved final IOP≤21 and >5 mm Hg without need for additional glaucoma procedures (qualified success), and 3 (4.8%) eyes achieved this without any medications (complete success). CME was the most common complication, occurring in 3 (4.8%) eyes. Among the 17 eyes that later needed additional glaucoma surgery or laser treatment, 14 had POAG, while 3 had CACG. The additional procedures included 9 selective laser trabeculoplasties, 3 Baerveldt tubes, 2 Ahmed tubes, 2 trabeculectomies, and 1 transscleral diode cyclophotocoagulation. Eyes with CACG had shorter follow-up (2.3±1.7 vs. 3.4±1.6 y, P=0.01), higher preoperative IOP (19.9±7.2 vs. 15.5±3.3 mm Hg, P=0.002), greater IOP reduction at 1 year and final follow-up (6.4±9.1 vs. 2.1±3.6 mm Hg, P=0.01 and 6.2±9.1 vs. 2.4±3.7 mm Hg, P=0.02, respectively), greater medication reduction at 1 year and final follow-up (0.9±1.3 vs. 0.2±1.0 medications, P=0.04 and 0.9±1.2 vs. 0.3±1.2 medications, P=0.05, respectively), and worse logMAR VA at 1 year and final follow-up (0.28±0.29 vs. 0.14±0.20, P=0.03 and 0.28±0.30 vs. 0.14±0.17, P=0.02, respectively).

Treatment Responses to Endocyclophotocoagulation for the Entire Study Population of 63 Eyes

Table 3 summarizes the results of IOP reduction univariate statistical analyses for the entire study population. By far, the strongest predictor of IOP reduction at 1 year and final follow-up was greater preoperative IOP (Fig. 1 and Table 3). Other variables significantly but less strongly associated with greater decrease in IOP after ECP included greater spherical equivalent refractive error, lower cup to disc ratio, CACG instead of POAG, and lower ECP power (Table 3). In multivariable modeling for decrease in IOP, after serial elimination of variables with P>0.15, greater preoperative IOP was the only variable associated with greater decrease in IOP (coefficient±SE 0.87±0.11, P=7.8×10−11 at 1 year and 0.98±0.08, P=2.4×10−17 at final follow-up). There was no difference in IOP reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5 mm Hg, respectively, P=0.18) and final follow-up (3.3, 4.8, 0.7 mm Hg, P=0.11).

Risk Factors for Intraocular Pressure Reduction After Endocyclophotocoagulation: Univariate Statistical Analyses of the Entire Study Population
Relationship between IOP before and after endocyclophotocoagulation. IOP indicates intraocular pressure.

Table 4 summarizes results of medication reduction univariate statistical analyses for the entire study population. The strongest predictor of decrease in number of medications at 1 year and final follow-up was greater preoperative number of medications. Other variables significantly but less strongly associated with greater decrease in number of medications included CACG instead of POAG and greater preoperative IOP. In multivariable modeling for decrease in medications, after serial elimination of variables with P>0.15, preoperative number of medications and preoperative IOP were the only statistically significant predictors at 1 year (coefficient±SE 0.33±0.12, P=0.01 and 0.06±0.02, P=0.03, respectively) and final follow-up (coefficient±SE 0.40±0.13, P=0.003 and 0.05±0.03, P=0.04, respectively). There was no difference in medication reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (0.3, 0.6, 0.4 medications, respectively, P=0.58) and final follow-up (0.1, 0.8, 0.4 medications, P=0.14).

Risk Factors for Medication Reduction After Endocyclophotocoagulation: Univariate Statistical Analyses of the Entire Study Population

Of the variables that were significantly associated with both greater phaco/ECP IOP lowering and medication reduction, the common predictors of greater phaco/ECP efficacy were CACG versus POAG and greater preoperative IOP (Table 3 and Table 4).


In this study of a patient population that had mostly well-controlled glaucoma and was undergoing ECP in combination with cataract extraction, phaco/ECP reduced IOP, and medication use to a greater degree in eyes with CACG than in eyes with POAG, and the treatment was comparably effective in all stages of glaucoma. These findings could be partially or entirely due to concurrent cataract extraction and greater CACG preoperative IOP. Higher preoperative IOP was strongly correlated with greater postoperative IOP decrease (Table 3), similar to the findings of a study that examined the impact of phacoemulsification in eyes with controlled open-angle glaucoma.14 The difference in IOP response following phaco/ECP between CACG and POAG in our study was largely driven by the higher preoperative IOP of CACG eyes compared with the preoperative IOP of POAG eyes (19.9 vs. 15.5 mm Hg, P=0.002). Eyes with CACG and POAG had similar final IOP (13.6 vs. 13.1 mm Hg, respectively, P=0.57), but the CACG group was able to achieve a greater IOP reduction from a higher baseline IOP despite a greater reduction in number of medications used after ECP (0.9 vs. 0.3 medications, P=0.05), even though there was a relatively similar preoperative number of medications (3.1 for CACG vs. 2.6 for POAG, P=0.07). In addition, of the 17 eyes that later needed additional glaucoma surgery or laser treatment during follow-up, 14 had POAG, while 3 had CACG, suggesting that phaco/ECP was a more definitive treatment for CACG than for POAG.

Phaco/ECP was performed by 9 different surgeons in this study, but there was no significant association of IOP or medication reduction with ECP degrees treated, power, or postoperative nonsteroidal anti-inflammatory drug and steroid regimens, other than an association between greater ECP power and lesser IOP response at 1 year, which did not remain significant in multivariable modeling. This finding of greater power producing lesser IOP response is somewhat counterintuitive, but it is possible that surgeons chose higher power for glaucoma that they anticipated being more refractory to treatment.

Phaco/ECP was found to be equally efficacious regardless of severity of glaucoma. Decreasing production of aqueous humor by ECP is applicable to any eye, unlike some minimally invasive glaucoma surgery procedures which target the trabecular meshwork or traditional outflow pathways and are generally thought to be most effective in mild to moderate glaucoma.15,16

Phaco/ECP was generally well tolerated, with few complications. Fewer postoperative ECP complications were noted in this study compared with earlier reports, which may be due to the comparatively lower treatment power used at our institution (ie, 150 to 500 mW) relative to the higher powers used in earlier iterations of ECP (ie, 500 to 900 mW). For example, Chen et al17 found 24% with postoperative fibrin exudate, 12% with hyphema, and 10% with CME. Of note, Chen and colleagues reported ECP results for CACG versus POAG patients that contradict the findings of our study. In that earlier study of refractory glaucoma, the authors reported that there were no differences in IOP response or final IOP based on underlying diagnosis based on 11 eyes with CACG and 16 eyes with POAG. The smaller sample size, greater laser power, and more refractory nature of the eyes in their study may contribute to the differences in results. Their CACG patients had preoperative IOP of 34.4 mm Hg, and their POAG patients had preoperative IOP of 21.3 mm Hg, both higher than that in our study (19.9 mm Hg for CACG and 15.5 mm Hg for POAG). Other studies could not adequately assess whether glaucoma type influenced ECP’s efficacy because other studies have often focused on strictly open-angle glaucoma or had too few CACG patients, such as the 6 CACG eyes of 84 eyes in a recent report on ECP combined with phacoemulsification.18

Morales et al7 also reported results that do not match ours, although they used similar ECP power of 200 to 490 mW and 180 to 270 degrees of treatment. They found that there was a trend toward success rates being higher in patients with POAG than in CACG, but these results were not statistically significant. They did not specify the definitions of POAG and CACG and did not mention gonioscopy, thus it is possible that their CACG population differed from ours. Unlike our study of all stages of glaucoma, their study focused only on advanced glaucoma, defined as “cup to disc ratio >0.7 with typical glaucomatous neuroretinal rim changes and accompanying visual field loss involving 1 or both hemifields on Humphrey or Goldman visual fields,” and 73% of eyes were on ≥3 medications. They used strict success criteria of a 15 mm Hg cutoff or 30% reduction of IOP from baseline, finding low absolute success rates for POAG (16%) and angle closure (13.6%). They reported higher qualified success rates of 72% for POAG and 42% for angle closure, but 46% of all eyes remained on >3 medications, compared with 75% which were on >3 medications preoperatively. It is possible that part of the reason for the difference in results between Morales et al and the current study is the focus on more advanced glaucoma requiring more medications at baseline. In advanced CACG, trabecular meshwork damage and peripheral anterior synechiae may be too far advanced to benefit much from the potential angle widening effect of phaco/ECP, that is, the synechiae may persist such that the angle remains closed after phaco/ECP, or even if the angle is opened, there may be other irreversible structural damage to the drainage outflow pathway; unfortunately, postoperative gonioscopy was not consistently documented in this study’s medical records. The present study included only 12 eyes that were characterized as having advanced glaucoma, and it is possible that eyes with advanced POAG and CACG respond differently to phaco/ECP than eyes with milder glaucoma. As reported in Table 3, this study found that IOP reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5 mm Hg, respectively, P=0.18) and final follow-up (3.3, 4.8, 0.7 mm Hg, P=0.11) showed trends toward less efficacy in advanced glaucoma, although the results were not statistically significant.

Phaco/ECP may be more effective at decreasing IOP in some cases of CACG than in POAG because it shrinks the ciliary processes and opens up the previously closed drainage angle anatomy in CACG, particularly in plateau iris configuration, and ultrasound biomicroscopy provides imaging support for this hypothesis.11,12 By decreasing the volume occupied by the ciliary body, ECP may provide space for the iris to fall posteriorly, creating room for the drainage angle to become more favorable for egress of aqueous fluid. This may also put the trabecular meshwork on stretch as it extends posteriorly, decreasing resistance to outflow, similar to changes caused by pilocarpine and argon laser trabeculoplasty. Only 3 cases in our preliminary chart review had plateau iris components recorded, and therefore they were not included in the current study due to the small sample size that was inadequate to evaluate whether plateau iris responded differently than typical CACG. However, analysis of this small number of cases suggested that plateau iris generally seemed to respond similarly to CACG, with preoperative IOP of 19.7 mm Hg on 3.3 medications, 13.0 mm Hg on 1.7 medications at postoperative year 1, and 13.7 mm Hg on 2.0 medications at final follow-up. Another possible explanation for the greater efficacy of phaco/ECP in CACG than in POAG is that patients with CACG may have less aqueous production than patients with OAG, possibly due to less baseline outflow through a chronically obstructed outflow pathway. ECP may be more effective in decreasing this small amount of aqueous production in CACG than the larger amount in OAG. However, further study is necessary to evaluate this theory.

In this retrospective study, the lack of a matched control group consisting of cataract surgery alone without concurrent ECP is important, and perhaps the differential effect of phaco/ECP in CACG versus POAG was partially or potentially entirely attributable to the effect of cataract extraction instead of ECP, in light of how the EAGLE study has demonstrated the efficacy of cataract extraction in CACG.19 Francis et al10 reported results from a prospective nonrandomized matched control study of combined phacoemulsification with ECP versus phacoemulsification alone in medically controlled open-angle glaucoma, which suggested that ECP had an additive effect on top of cataract extraction based on the finding that the combined procedure had 2.1 mm Hg IOP decrease and 1.1 medication decrease compared with 0.8 mm Hg and 0.4 medication decrease for standalone cataract surgery. Of note, while the preoperative IOP was matched, the preoperative medication usage was almost a full drop greater in the phacoemulsification alone group (2.4 vs. 1.5 medications). This could suggest more difficult to treat glaucoma in the phacoemulsification alone group, leaving the possibility open that underlying eye characteristics were the cause of different responses to surgery, not the type of surgery itself. Although the study was prospective, it was nonrandomized and therefore subject to selection bias, as acknowledged by the authors, but they noted that the decision to add ECP to phacoemulsification was mostly based on availability of the ECP device at the time of surgery and patient preference, not eye characteristics.

A separate retrospective review of combined phacoemulsification and ECP procedures compared with standalone phacoemulsification case-matched controls also suggested that adding ECP confers a decrease in 1 topical medication but no significant decrease in IOP, although this study of 313 eyes only included 5 eyes with CACG.20 To our knowledge, there are no studies of whether addition of ECP to phacoemulsification in CACG provides additional benefit on top of phacoemulsification, and in preliminary identification of eligible eyes for this study, only 2 of the eyes that underwent standalone ECP had CACG, preventing any meaningful analysis of this question. A meta-analysis of phacoemulsification in glaucoma did report that CACG eyes had mean preoperative IOP of 20.2 mm Hg on 1.9 medications and decreased postoperatively to 14.2 mm Hg on 0.8 medications, while POAG eyes had mean preoperative IOP of 17.7 mm Hg on 1.7 medications and decreased postoperatively to 15.4 mm Hg on 1.5 medications.21 However, the eyes in the current study had more advanced glaucoma than these historical controls, making comparison difficult. Notably, there have been studies of standalone phacoemulsification in medically controlled and uncontrolled CACG showing IOP and medication lowering efficacy nearly comparable with that found in this study of phaco/ECP.22–24 In controlled CACG, preoperative IOP of 16.3 mm Hg on 2.2 medications decreased to 14.3 mm Hg on 0.8 medications at 1 year and 14.5 mm Hg on 1.1 medications at 2 years after phacoemulsification.22 In uncontrolled CACG with higher mean baseline IOP and baseline medication usage than in the present study, a study of eyes with cataracts reported preoperative IOP of 24.4 mm Hg on 3.3 medications that decreased to 15.5 mm Hg on 1.5 medications at 1 year and 16.1 mm Hg on 1.7 medications at 2 years; clear lens extraction in CACG without cataract reported similar decrease in IOP and medications.23,24

This study is limited by the fact that it is a retrospective chart review, subject to issues that include patient selection biases, incomplete and nonstandard data recording (eg, partial missing visual field mean deviation data to assess glaucoma severity, no minimum visual field reliability criteria), and lack of a standard algorithm for adjusting glaucoma medications postoperatively or when to assess for CME by optical coherence tomography. Furthermore, the multivariable modeling helped to control for confounding factors, but it was limited in utility because of the outsized effect of preoperative IOP and number of medications (Tables 3 and 4).

A standalone ECP control group without concurrent phacoemulsification may have provided additional information, but in preliminary review of eyes that had billing codes for ECP, there were 13 eyes that underwent standalone ECP without concurrent phacoemulsification, but these eyes were not included in the present study because of the small number of cases and because they had higher preoperative IOP despite being on slightly high numbers of medications (21.3 vs. 17.0 mm Hg on 3.4 vs. 2.8 medications). Standalone ECP eyes had much greater decreases in IOP than eyes that underwent phaco/ECP (9.1 vs. 3.6 mm Hg at postoperative year 1). This suggests that the primary goal in eyes that underwent standalone ECP was better control of refractory glaucoma, while the goal in combined phaco/ECP eyes was to add on a procedure to reduce medication use at the time of a cataract surgery that may have been scheduled for visual rehabilitation purposes that were independent of IOP control issues.

Future study is needed to determine the extent to which the differential effect of phaco/ECP in CACG and POAG on IOP and medication decrease seen in this study was dependent on the higher CACG preoperative IOP and the effect of cataract extraction compared with the effect of ECP. A prospective randomized trial of patients with CACG and POAG randomized to phaco/ECP versus phacoemulsification alone could help address these questions. Nevertheless, these results indicate that phaco/ECP is a safe and effective surgical option that may be a consideration in CACG, and it can be used with comparable success in all stages of glaucoma.


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endoscopic cyclophotocoagulation; endocyclophotocoagulation; ECP

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.